Differentiating and antitumor activities of 1 alpha,25-dihydroxyvitamin D3 in vitro and 1 alpha-hydroxyvitamin D3 in vivo on human osteosarcoma

Abstract

The differentiating and antitumor activities of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in vitro and 1α-hydroxyvitamin D3 (1α(OH)D3) in vivo were studied with a human osteosarcoma cell line (OST strain).

Antitumor activity was estimated with the use of 3-(4,5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide (MTT) assay, colony-forming assay, and athymic mouse assay.

The intracellular alkaline phosphatase (ALP) activity of tumor cells and production of bone Gla protein (BGP) in culture media were measured to mark osteoblastic differentiation.

In addition, the combination of 1α,25(OH)2D3 and cis-dichlorodiammineplatinum(II) (CDDP) was tested by the colony-forming assay and the measurement of ALP activity and BGP production for differentiating and antitumor effects.

The assays revealed that 1α,25(OH)2D3 exerted a dose-related, growth-inhibitory influence. In the colony-forming assay, the 1α,25(OH)2D3-treated colonies were smaller than the untreated colonies.

The ALP activity and the BGP production also increased in relation to dose. In the assay in athymic mice, the relative weight of tumors treated with 1α(OH)D3 at 2.5 nmol/kg was significantly smaller than that of the controls, and no side effects were observed in the 1α(OH)D3-treated mice.

Marked tumor chondrogenesis was observed in human osteosarcoma treated with 1α(OH)D3 in athymic mice. The combination of 1α,25(OH)2D3 at 10−8 M and CDDP at 2 μg/ml significantly enhanced both the differentiation and the growth inhibition in vitro.

Our study apparently is the first demonstration that vitamin D3 metabolites have an antitumor and differentiating effect on human osteosarcoma cells in vitro and in athymic mice. Vitamin D3 should be examined further to discover whether it could be a useful drug in hormonal treatment for human osteosarcomas.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Variable Part - Chondroitin sulfate, up to 3-4 grams per day, orally);

- A retrospective observational study on cases of Osteosarcomas treated with a multitherapy: The rationale and effectiveness;

- A Retrospective Observational Study on Cases of Sarcoma Treated with the Di Bella Method: Rationale and Effectiveness;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis.